1,726,616 research outputs found

    Old Jazz Meeting

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    Wer will huldigen? Ick nich! Wer noch? Ick bin en Preuße! Kennst Du meine Fäuste?

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    WER WILL HULDIGEN? ICK NICH! WER NOCH? ICK BIN EN PREUSSE! KENNST DU MEINE FÄUSTE? Wer will huldigen? Ick nich! Wer noch? Ick bin en Preuße! Kennst Du meine Fäuste? (Public Domain) (1

    A novel ICK mutation causes ciliary disruption and lethal endocrine-cerebro-osteodysplasia syndrome

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    Full author list omitted for brevity. For full list of authors see article.BACKGROUND: Endocrine-cerebro-osteodysplasia (ECO) syndrome [MIM:612651] caused by a recessive mutation (p.R272Q) in Intestinal cell kinase (ICK) shows significant clinical overlap with ciliary disorders. Similarities are strongest between ECO syndrome, the Majewski and Mohr-Majewski short-rib thoracic dysplasia (SRTD) with polydactyly syndromes, and hydrolethalus syndrome. In this study, we present a novel homozygous ICK mutation in a fetus with ECO syndrome and compare the effect of this mutation with the previously reported ICK variant on ciliogenesis and cilium morphology. RESULTS: Through homozygosity mapping and whole-exome sequencing, we identified a second variant (c.358G > T; p.G120C) in ICK in a Turkish fetus presenting with ECO syndrome. In vitro studies of wild-type and mutant mRFP-ICK (p.G120C and p.R272Q) revealed that, in contrast to the wild-type protein that localizes along the ciliary axoneme and/or is present in the ciliary base, mutant proteins rather enrich in the ciliary tip. In addition, immunocytochemistry revealed a decreased number of cilia in ICK p.R272Q-affected cells. CONCLUSIONS: Through identification of a novel ICK mutation, we confirm that disruption of ICK causes ECO syndrome, which clinically overlaps with the spectrum of ciliopathies. Expression of ICK-mutated proteins result in an abnormal ciliary localization compared to wild-type protein. Primary fibroblasts derived from an individual with ECO syndrome display ciliogenesis defects. In aggregate, our findings are consistent with recent reports that show that ICK regulates ciliary biology in vitro and in mice, confirming that ECO syndrome is a severe ciliopathy

    Colorectal cancer screening and perceived disgust: the importance of the “ICK” factor in Faecal Occult Blood Test uptake

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    Background: Colorectal cancer is a major cause of cancer deaths worldwide. Screening is key to early detection but uptake of national programmes is poor, especially amongst those from lower socio-economic backgrounds. Decisions not to take up screening may be based more on emotional rather than rational evaluations. We aimed to examine the importance of perceived disgust (the ‘ICK’ factor) in determining colorectal cancer screening uptake, in a large, randomised controlled trial. Methods: This paper reports secondary analysis of a randomised controlled trial of a simple, questionnaire-based Anticipated Regret (AR) intervention, which was delivered alongside existing pre-notification letters. 60,000 adults aged 50- 74 who were participant in the Scottish National Screening programme were randomised to one of 3 treatment arms: 1) no questionnaire (control), 2) Health Locus of Control (HLOC) questionnaire or 3) AR questionnaire. Primary outcome was Faecal Occult Blood Test kit return (FOBT uptake). 13,645 people completed questionnaires of secondary outcomes including intention to return test kit and a new self-report measure of perceived disgust (ICK-C). Results: Intentions, ICK and AR were all predictors of FOBT uptake; however, for people who expressed strong intentions to return their FOBT kit, only ICK differentiated kit returners from non-returners, with non-returners reporting higher disgust (mean difference=0.51; 95% CI for difference (0.37, 0.64), Cohen’s d=0.34). The 4-item ICK-C showed excellent internal reliability and predictive validity with regard to an objective measure i.e., FOBT uptake. Conclusions: The findings show that perceived disgust is an important emotional psychological construct in determining uptake of colorectal cancer screening. We also demonstrated that a simple 4-item scale (the ‘ICK-C), developed to be used in research on colorectal cancer screening, has excellent psychometric properties

    ICK and MOK control cilium length.

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    <p>(A) Immunoblot of cell lysates of IMCD-3 cells transduced with shRNA constructs targeting ICK and MOK. Actin was used as loading control. (B) Average length of primary cilia of IMCD-3 cells depleted of ICK. (C) Average length of primary cilia of IMCD-3 cells depleted of MOK. (D) Average length of primary cilia of IMCD-3 cells depleted of ICK and MOK, combining ICKsh #01 and MOKsh #01 or ICKsh #02 and MOKsh #02. (E) Immunofluorescence images of IMCD-3 cells expressing control shRNA, ICKsh #01, or MOKsh #01 stained with anti-acetylated tubulin. Scale bar 10 µm. (F) Average length of primary cilia of IMCD-3 cells overexpressing GFP-C1, wild type (wt) or kinase-dead (kd) GFP-ICK, or GFP-MOK. (G) Immunofluorescence images of IMCD-3 cells expressing GFP-C1, wt or kd GFP-ICK, or GFP-MOK stained with anti-acetylated tubulin. Scale bar 1 µm. Numbers in the red bars indicate number of cilia measured. Data were obtained in at least 2 independent experiments. Statistically significant differences (p<0.001) compared to control cells are indicated with a black asterisk. Error bars indicate SD.</p

    Kasper-Ohm un ick

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    Disse näie Uplaag (1944) van de Utgaav van 1867/68 van John Brinckmans "Kasper Ohm un ick" hört to de plattdütsken Seekant-Romans. Dat fallt up, dat Brinkmann en Roman van 214 Sieden nich in Kapitels indäilen deit..(St.D.) <dt.

    The "Ick" Factor, Anticipated Regret, and Willingness to Become an Organ Donor

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    Objective: This research tested the role of traditional rational-cognitive factors and emotional barriers to posthumous organ donation. An example of an emotional barrier is the "ick" factor, a basic disgust reaction to the idea of organ donation. We also tested the potential role of manipulating anticipated regret to increase intention to donate in people who are not yet registered organ donors. Design: In three experiments involving 621 members of the United Kingdom general public, participants were invited to complete questionnaire measures tapping potential emotional affective attitude barriers such as the "ick" factor, the desire to retain bodily integrity after death, and medical mistrust. Registered posthumous organ donors were compared with nondonors. In Experiments 2 and 3, nondonors were then allocated to a simple anticipated regret manipulation versus a control condition, and the impact on intention to donate was tested. Main Outcome Measures: Self-reported emotional barriers and intention to donate in the future. Results: Traditional rational-cognitive factors such as knowledge, attitude, and subjective norm failed to distinguish donors from nondonors. However, in all three experiments, nondonors scored significantly higher than donors on the emotional "ick" factor and bodily integrity scales. A simple anticipated regret manipulation led to a significant increase in intention to register as an organ donor in future. Conclusions: Negative affective attitudes are thus crucial barriers to people registering as organ donors. A simple anticipated regret manipulation has the potential to significantly increase organ donation rates

    Overexpression of ICK results in decreased retrograde IFT velocity.

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    <p>(A) Representative example of kymograph of GFP-ICK in IMCD-3 cells. The basal body (b.b.) and the distal tip (d.t.) of the cilium are indicated. In the corresponding drawing anterograde trajectories are shown in red, and retrograde trajectories are shown in blue. (B) Representative example of kymograph of GFP-MOK in IMCD-3 cells. The basal body (b.b.) and the distal tip (d.t.) of the cilium are indicated. In the corresponding drawing anterograde trajectories are shown in red, and retrograde trajectories are shown in blue. (C) Average anterograde velocities of wt or kd GFP-ICK or GFP-MOK. (D) Average retrograde velocities of wt or kd GFP-ICK or GFP-MOK. The velocity of GFP-ICK is statistically significantly different (p<0.001) from those of GFP-ICKkd and wt or kd GFP-MOK (indicated with a black asterisk). Error bars indicate SD. Numbers in the bars indicate number of particles analyzed.</p

    Ccrk-Mak/Ick signaling is a ciliary transport regulator essential for retinal photoreceptor survival

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    Chaya T., Maeda Y., Tsutsumi R., et al. Ccrk-Mak/Ick signaling is a ciliary transport regulator essential for retinal photoreceptor survival. Life science alliance 7, (2024); https://doi.org/10.26508/lsa.202402880.Primary cilia are microtubule-based sensory organelles whose dysfunction causes ciliopathies in humans. The formation, function, and maintenance of primary cilia depend crucially on intraflagellar transport (IFT); however, the regulatory mechanisms of IFT at ciliary tips are poorly understood. Here, we identified that the ciliopathy kinase Mak is a ciliary tip-localized IFT regulator that cooperatively acts with the ciliopathy kinase Ick, an IFT regulator. Simultaneous disruption of Mak and Ick resulted in loss of photoreceptor ciliary axonemes and severe retinal degeneration. Gene delivery of Ick and pharmacological inhibition of FGF receptors, Ick negative regulators, ameliorated retinal degeneration in Mak-/- mice. We also identified that Ccrk kinase is an upstream activator of Mak and Ick in retinal photoreceptor cells. Furthermore, the overexpression of Mak, Ick, and Ccrk and pharmacological inhibition of FGF receptors suppressed ciliopathy-related phenotypes caused by cytoplasmic dynein inhibition in cultured cells. Collectively, our results show that the Ccrk-Mak/Ick axis is an IFT regulator essential for retinal photoreceptor maintenance and present activation of Ick as a potential therapeutic approach for retinitis pigmentosa caused by MAK mutations
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